Adverse Childhood Experiences, Epigenetic Measures, and Obesity in Youth.
Adverse Childhood Experiences, Epigenetic Measures, and Obesity in Youth.
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DOI：
10.1016/j.jpeds.2018.06.051
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Hudziak J
中科院分区：
文献类型：
--
作者：
Kaufman J;Montalvo-Ortiz JL;Holbrook H;O'Loughlin K;Orr C;Kearney C;Yang BZ;Wang T;Zhao H;Althoff R;Garavan H;Gelernter J;Hudziak J
确定不良童年经历和 DNA 甲基化的测量是否与青少年肥胖指数相关。参与者来自 321 名 8 至 15 岁儿童队列，该队列是为了调查受虐待儿童的风险、复原力和精神结果而招募的。对 234 名参与者（56% 为女性；52% 受到虐待）的肥胖评估作为附加数据收集。 Illumina 阵列用于检查唾液 DNA 中肥胖的全基因组表观遗传预测因子。出于分析目的，第一批分析的队列包括发现样本 (n = 160)，第二批分析的队列包括复制样本 (n = 74)。在控制种族、性别、年龄、细胞异质性、3个主要成分和全基因组测试后，发现10个甲基化位点与不良童年经历相互作用，以预测体重指数的横断面测量，并且发现另外6个位点在预测体重指数方面发挥主要作用（P < 5.0 × 10−7，所有比较）。其中八个甲基化位点位于先前与肥胖风险相关的基因中（例如，PCK2、CxCl10、BCAT1、HID1、PRDM16、MADD、PXDN、GALE），发现数据集中的一些发现在第二组中得到了重复。这项研究为未来的纵向研究奠定了基础，以进一步阐明这些机制并确定新的干预措施以减轻与早期逆境相关的健康负担。
To determine if measures of adverse childhood experiences and DNA methylation relate to indices of obesity in youth. Participants were derived from a cohort of 321 8 to 15-year-old children recruited for an investigation examining risk and resilience and psychiatric outcomes in maltreated children. Assessments of obesity were collected as an add-on for a subset of 234 participants (56% female; 52% maltreated). Illumina arrays were used to examine whole genome epigenetic predictors of obesity in saliva DNA. For analytic purposes, the cohort analyzed in the first batch comprised the discovery sample (n = 160), and the cohort analyzed in the second batch the replication sample (n = 74). After controlling for race, sex, age, cell heterogeneity, 3 principal components, and whole genome testing, 10 methylation sites were found to interact with adverse childhood experiences to predict cross-sectional measures of body mass index, and an additional 6 sites were found to exert a main effect in predicting body mass index (P < 5.0 × 10−7, all comparisons). Eight of the methylation sites were in genes previously associated with obesity risk (eg, PCK2, CxCl10, BCAT1, HID1, PRDM16, MADD, PXDN, GALE), with several of the findings from the discovery data set replicated in the second cohort. This study lays the groundwork for future longitudinal studies to elucidate these mechanisms further and identify novel interventions to alleviate the health burdens associated with early adversity.
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